Temozolomide (TMZ) is an alkylating anti-tumor drug containing an imidazotetrazine ring with an anti-tumor activity. Its chemical structure is presented as follows:

Temozolomide belongs to a pro-drug with no activity. It is usually converted to the active compound MITC (5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide) under a physiological pH level via a non-enzymatic pathway, and MITC is further hydrolyzed to an active metabolite, showing its anti-tumor activity. In theory, the anti-tumor activity of MTIC is mainly produced by major DNA alkylation (methylation) with the 6th oxygen atom of guanine. Also, it can have secondary additional alkylation with the 7th nitrogen atom of guanine. Therefore, the subsequent cytotoxicity is considered to have the relationship with these abnormally-repaired methyl compounds.
Temozolomide compounds have been already synthesized. In recent years, however, it is continuously found that its new crystalline forms have excellent medicinal value. For example, U.S. Pat. No. 5,260,291 disclosed Temozolomide polymorphs prepared by using the following three different solvent systems: acetone and water (3:1), acetone and water (1:3), and water. Chinese Journal of Pharmaceuticals reproduced the method of U.S. Pat. No. 5,260,291, and reported the relevant data; US 20050187206 disclosed the methods for preparing various crystalline forms of Temozolomide by using a variety of solvents, such as pyridine, ethanol, acetone etc.; WO2008111092 disclosed Temozolomide monohydrate, prepared by the solvent of acetone and water (3:1); Chinese patent CN201110201186.3 disclosed a type of crystalline form of Temozolomide prepared by using a mixed solvent of acetone, acetonitrile and water.
The afore-mentioned methods have a problem caused by the solubility of TMZ, i.e. a large amount of solvent, which is up to a few times or even hundreds of times of Temozolomide, are required for dissolution, for example, in US20050187206, the amount of ethanol reached 270 times the amount of Temozolomide (v/w), and the amount of acetone used even reached more than 300 times the amount of Temozolomide (v/w). Alternatively, although the volume of the solvent is more than 10 times the amount of Temozolomide, the yield is low, thus it is unsuitable for industrial production. In addition, the crystalline forms prepared by the above-mentioned methods are unstable, e.g. in US20050187206, crystalline Form I of Temozolomide was transformed into crystalline Form II under a condition of being heated to approximately 30° C.
Therefore, it is necessary to find a stable crystalline form of Temozolomide for medicine application, specifically as an active pharmaceutical ingredient (API) in a solid pharmaceutical. In addition, the solvents used in the recrystallization methods of Temozolomide in the prior art were short of specificity, so that a small amount of impurities was contained in the obtained crystalline forms of Temozolomide. As a result, the application was affected.